imho the avenue they will go is "hard mode" essentially something between angels/bobs and vanilla + space exploration.
Official hard mode would instantly generate them money considering a/b is most downloaded mods comp ever.
I don't think they will expand sideways underground and so on.
Angel's and Bob's take a literally everything-and-the-kitchen-sink approach, though, and in my opinion they're what people download the most because they change up vanilla inputs and outputs (so you've got to re-learn/re-design, not depend on old blueprints, etc.) and essentially pad out the game. I fully acknowledge that they increase the game's level of "logistical puzzle challenge," by the way, which also adds many hours of playtime because you've got a lot more to do to get those buses moving and the end products flying out.
I don't think Wube will go this way at all, for several reasons, one of which is that there'll always be mods like Bob's and Angel's to pad out the game for those who want that sort of thing. Wube has always seemed more concerned with creating solid, broad foundations and functionally complete vanilla elegance at every tier of play, rather than cramming everything and the kitchen sink into every tier.
We like complexity, but there's such a thing as overcomplicating the baseline game with arbitrary minutiae. They've been very good at avoiding this while not oversimplifying, a great balance.